Several studies have shown that HER2 signaling interplays intimately with TGF-β/Smad in regulating mammary epithelial cell biology and breast cancer progression.512,513 The synergy between the TGF-β and HER2/RAS/MAPK signaling can induce the secretion of additional growth factors and cytokines, including TGF-β itself, which in turn induce EMT and tumor invasion.514,515 Wnt signaling benefits from extensive crosstalk with other signaling pathways, particularly TGF-β/bone morphogenic protein (BMP) signaling. The gene discussed is ERBB2; the disease is breast cancer.